PMID: 

Can J Physiol Pharmacol. 2019 Jul 24. Epub 2019 Jul 24. PMID: 31340128

Abstract Title: 

Effects of Resveratrol Postconditioning on Cerebral Ischemia in mice: Role of the Sirtuin-1 (SIRT1) Pathway.

Abstract: 

Evidence has demonstrated that resveratrol preconditioning exhibits neuroprotection against cerebral IR injury. The current investigation aimed to explore whether pharmacological postconditioning, by administering resveratrol, after a sustained ischemia&prior to prolonged reperfusion abrogates cerebral IR injury. Cerebral ischemia-reperfusion-induced injury mice model was employed in this study to evaluate the neuroprotective effects of pharmacological postconditioning (pPoCo) with resveratrol (30 mg/kg; i.p.) administered 5 mins before reperfusion. We administered Sirtinol, a SIRT1/2 selective inhibitor (10 mg/kg; i.p.) 10 min before ischemia (17 min) and reperfusion (24 h), to elucidate whether the neuroprotection with resveratrol postconditioning depends on SIRT1 activation. Various biochemical, behavioral parameters and histopathological changes were assessed to examine the effect of pPoCo. Infarct size is estimated using TTC staining. It was established that resveratrol postconditioning abrogated the deleterious effects of IR injury expressed with regard to biochemical parameters of oxidative stress (TBARS, SOD, GSH), acetylcholinestrase activity, behavioual parameters (memory, motor coordination), infarct size and histopathological changes. Sirtinol significantly reversed the effect of resveratrol PoCo. We conclude that induced neuroprotective benefits of resveratrol postconditiong may be the consequence of SIRT1 activation and resveratrol can be considered, for further studies, as potential agent inducing pharmacological postconditioning in clinical situations.

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PMID: 

Cancer Cell Int. 2019 ;19:180. Epub 2019 Jul 15. PMID: 31341423

Abstract Title: 

Resveratrol is a promising agent for colorectal cancer prevention and treatment: focus on molecular mechanisms.

Abstract: 

Colorectal cancer (CRC) is the third most common cancer and one of the main causes of cancer death entire the world. Environmental, dietary, and lifestyle factors including red meat consumption, cigarette smoking, alcohol intake and family history are the most important risk factors of CRC. Multiple pathways including inflammation, oxidative stress, and apoptosis are involved in its incidence and progression. Resveratrol, a polyphenolic compound, has different pharmacologic functions including anti-inflammation, cancer prevention, lipid-lowering effect, and hypoglycemic effect. Many studies have proved that resveratrol might also represent a chemo preventive effect on CRC. Thus, the aim of the current review is to depict the role of resveratrol in treatment of CRC in a molecular manner.

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PMID: 

Eur Rev Med Pharmacol Sci. 2019 Jul ;23(14):6352-6359. PMID: 31364143

Abstract Title: 

Resveratrol alleviates osteoporosis through improving the osteogenic differentiation of bone marrow mesenchymal stem cells.

Abstract: 

OBJECTIVE: To investigate the protective effect of Resveratrol (RES) on TNF-α-induced inhibition of osteogenic differentiation, thus alleviating the progression of osteoporosis (OP).MATERIALS AND METHODS: OP model in rats was first conducted by performing ovariectomy (OVX). Rats were randomly divided into sham group, OVX group, and RES+OVX group. Body weight of each rat was regularly recorded every week. Bone mineral density (BMD) of rat femoral metaphysis was measured by micro-CT. Changes in radial degrees and loads of rat femora were examined through three-point bending experiments. Relative levels of OCN and Runx2 in each group were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Alkaline phosphatase (ALP) activity and calcification ability were assessed through ALP staining and alizarin red staining, respectively. Bone mesenchymal stem cells (BMSCs) were extracted from healthy rats and divided into control group, Tumor necrosis factor-α (TNF-α) group, RES group, and TNF-α+RES group based on different treatments. Relative levels of OCN and Runx2, ALP activity, and calcification ability in each group were detected in the same way. Finally, protein levels of NF-κB and β-catenin in BMSCs were determined.RESULTS: Rats in each group gained body weight during the experimental period, especially those in OVX group and RES+OVX group. No significant difference in the body weight was found between OVX group and RES+OVX group. BMD in rat femora of RES+OVX group was higher than in OVX group but lower than sham group. Elastic/max radial degree and elastic/max load of femora were markedly reduced in OVX group compared to RES+OVX group. Relative levels of OCN and Runx2, ALP activity and calcification ability decreased in OVX group relative to sham group, which were partially reversed by RES treatment. After osteogenic differentiation in BMSCs induced with TNF-α, viability and calcification ability were markedly reduced and were upregulated by RES treatment. Moreover, RES treatment enhanced the downregulated levels of OCN and Runx2 in BMSCs undergoing TNF-α induction. Upregulated protein levels of nuclear factor kappa-B (NF-κB) and β-catenin in TNF-α-induced BMSCs were downregulated by RES treatment.CONCLUSIONS: The inhibited osteogenic differentiation of BMSCs undergoing TNF-α induction is improved by resveratrol treatment, which contributes to alleviate the progression of osteoporosis.

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PMID: 

Naunyn Schmiedebergs Arch Pharmacol. 2019 Jul 31. Epub 2019 Jul 31. PMID: 31367863

Abstract Title: 

Therapeutic effects of resveratrol in Escherichia coli-induced rat endometritis model.

Abstract: 

Endometritis is an inflammatory disorder of the endometrial lining of the uterine tissue in postpartum stage. Endometritis mostly progresses subclinically and causes infertility through the disruption of the hormonal balance. It has been shown in many studies that resveratrol has anti-inflammatory and antioxidant properties. However, the possible beneficial effects of resveratrol in endometritis have not been determined yet. The aim of the present study is to evaluate the treatment potential of resveratrol in an experimentally induced endometritis model in rats. Endometritis was induced in 12-week-old female, nonpregnant, Sprague Dawley rats. The animals were divided into six groups: control (NaCl 0.9%) and endometritis (NaCl 0.9%), marbofloxacin + PGF, marbofloxacin, marbofloxacin + resveratrol, and resveratrol groups. To induce endometritis, 5 mg/kg/s.c. progesterone was given for 5 days, and then Escherichia coli (50 μl, 1 × 10 cfu/rat) was injected in the right cornu uteri following laparotomy. Sixteen hours after bacterial inoculation, the treatment protocol was applied for 14 days. At the end of the experiment, the total oxidant status (TOS) and total antioxidant status (TAS) were examined spectrophotometrically in uterus tissues. The severity of inflammation in uterus samples and follicular activity in ovarian tissues were histopathologically evaluated. In addition, serum cytokine levels were determined. While TAS in uterine tissue significantly increased in the resveratrol group when compared to that of the other groups (p  0.05). The inflammation of the endometrium and the numbers of corpus luteum in the endometritis group were highly significant when compared to those of the other groups (p 

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PMID: 

Curr Alzheimer Res. 2019 Aug 1. Epub 2019 Aug 1. PMID: 31368873

Abstract Title: 

Resveratrol rescues tau-induced cognitive deficits and neuropathology in a mouse model of tauopathy.

Abstract: 

BACKGROUND: Alzheimer's disease (AD) is characterized by the presence of extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles assembled by the microtubule-associated protein tau. Increasing evidences demonstrated that tau pathology played an important role in AD progression. Resveratrol (RSV) has been previously proved to exert neuroprotective effect against AD byinhibiting Aβ generation and Aβ-induced neurocytotoxicity, while its effect on tau pathology is still unknown.METHOD: The effect of RSV on tau aggregation was measured by Thioflavin T fluorescence and Transmission electron microscope imaging; The effect of RSV on tau oligomer-induced cytotoxicity was assessed by MTT assay; The uptake of extracellular tau by N2a cells was determined by immunocytochemistry. 6-month-old male PS19 mice were treated with RSV or vehicle by oral administration (gavage) once a day for 5 weeks. The cognitive performance was determined using Morris water maze test, object recognition test and Y-maze test. The levels of phosphorylated-tau, gliosis, proinflammatory cytokines such as TNF-α and IL-1β, and synaptic proteins including synaptophysin and PSD95 in the mouse brains were evaluated by immunoblotting, immunostaining and ELISA, respectively.RESULTS: RSV significantly inhibited tau aggregation and tau oligomer-induced cytotoxicity, and blocked the uptake of extracellular tau oligomers by N2a cells. When applied to PS19 mice, RSV treatment effectively rescued cognitive deficits, reduced the levels of phosphorylated tau, neuroinflammation and synapse loss in the brains of mice.CONCLUSION: These findings suggest that RSV has promising therapeutic potential for AD and other tauopathies.

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PMID: 

Nutrients. 2019 Jul 31 ;11(8). Epub 2019 Jul 31. PMID: 31370365

Abstract Title: 

Role of Resveratrol and Selenium on Oxidative Stress and Expression of Antioxidant and Anti-Aging Genes in Immortalized Lymphocytes from Alzheimer's Disease Patients.

Abstract: 

Oxidative damage is involved in the pathophysiology of age-related ailments, including Alzheimer's disease (AD). Studies have shown that the brain tissue and also lymphocytes from AD patients present increased oxidative stress compared to healthy controls (HCs). Here, we use lymphoblastoid cell lines (LCLs) from AD patients and HCs to investigate the role of resveratrol (RV) and selenium (Se) in the reduction of reactive oxygen species (ROS) generated after an oxidative injury. We also studied whether these compounds elicited expression changes in genes involved in the antioxidant cell response and other aging-related mechanisms. AD LCLs showed higher ROS levels than those from HCs in response to HOand FeSOoxidative insults. RV triggered a protective response against ROS under control and oxidizing conditions, whereas Se exerted antioxidant effects only in AD LCLs under oxidizing conditions. RV increased the expression of genes encoding known antioxidants (catalase, copper chaperone for superoxide dismutase 1, glutathione S-transferase zeta 1) and anti-aging factors (sirtuin 1 and sirtuin 3) in both AD and HC LCLs. Our findings support RV as a candidate for inducing resilience and protection against AD, and reinforce the value of LCLs as a feasible peripheral cell model for understanding the protective mechanisms of nutraceuticals against oxidative stress in aging and AD.

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PMID: 

J Trauma Acute Care Surg. 2019 Aug 5. Epub 2019 Aug 5. PMID: 31389921

Abstract Title: 

Role of Resveratrol in Protecting Vasodilatation Function in Septic Shock Rats and its Mechanism.

Abstract: 

BACKGROUND: Vascular dysfunction is a major cause of sepsis-induced multiple-organ dysfunction. Resveratrol is a polyphenol compound with extensive pharmacological effects including anti-inflammation. The aim of this study was to determine the role and mechanism of resveratrol in protecting vascular function following sepsis.METHODS: The cecal ligation and puncture (CLP) method was used to establish a septic shock rat model. Resveratrol (5mg/kg and 10mg/kg) was administered intravenously immediately and at 12h after CLP, respectively. The effects of resveratrol on vasodilatation function, blood flow velocity, hemodynamics, and vital organ function and its relationship to Rac-1 and HIF-1α were observed.RESULTS: Vascular relaxation reactivity and blood flow velocity were significantly decreased after septic shock, both were significantly improved by resveratrol 5mg/kg and 10mg/kg, and the effect of 10mg/kg was greater. The relaxation reactivity of the superior mesenteric artery (SMA) to acetylcholine (Ach) was increased by 43.2%. The blood flow velocity of mesenteric arterioles and venules was increased by 47.1% and 51%, respectively, after resveratrol (10mg/kg) administration compared with the septic shock group. The hemodynamics and both liver and kidney blood flow were significantly decreased after septic shock, which were significantly improved them by resveratrol, which enhanced the vascular relaxation reactivity in septic shock rats. The 72h survival rate of septic shock rats in the resveratrol group (62.5%) was significantly higher than that in the septic shock group (6.3%). Resveratrol significantly up-regulated the expression of eNOS and down-regulated the expression of iNOS, Rac-1 and HIF-1α. Inhibitors of Rac-1 and HIF-1α significantly improved the expression of eNOS, and inhibition of eNOS (L-NAME,5mg/kg) antagonized the resveratrol-induced improvement in vascular relaxation reactivity and survival.CONCLUSION: Resveratrol was beneficial for vasodilatation function in rats with septic shock, which is the major contribution to resveratrol improving hemodynamics and organ perfusion. The mechanism involved resveratrol up-regulating the expression of eNOS by inhibiting Rac-1 and HIF-1α.LEVEL OF EVIDENCE: therapeutic study, level II.

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PMID: 

Arh Hig Rada Toksikol. 2017 Jun 27 ;68(2):142-152. PMID: 28665795

Abstract Title: 

Electromagnetic fields at a mobile phone frequency (900 MHz) trigger the onset of general stress response along with DNA modifications in Eisenia fetida earthworms.

Abstract: 

Eisenia fetida earthworms were exposed to electromagnetic field (EMF) at a mobile phone frequency (900 MHz) and at field levels ranging from 10 to 120 V m-1 for a period of two hours (corresponding to specific absorption rates ranging from 0.13 to 9.33 mW kg-1). Potential effects of longer exposure (four hours), field modulation, and a recovery period of 24 h after two hours of exposure were addressed at the field level of 23 V m-1. All exposure treatments induced significant DNA modifications as assessed by a quantitative random amplified polymorphic DNA-PCR. Even after 24 h of recovery following a two hour-exposure, the number of probe hybridisation sites displayed a significant two-fold decrease as compared to untreated control earthworms, implying a loss of hybridisation sites and a persistent genotoxic effect of EMF. Expression of genes involved in the response to general stress (HSP70 encoding the 70 kDa heat shock protein, and MEKK1 involved in signal transduction), oxidative stress (CAT, encoding catalase), and chemical and immune defence (LYS, encoding lysenin, and MYD, encoding a myeloid differentiation factor) were up-regulated after exposure to 10 and modulated 23 V m-1 field levels. Western blots showing an increased quantity of HSP70 and MTCO1 proteins confirmed this stress response. HSP70 and LYS genes were up-regulated after 24 h of recovery following a two hour-exposure, meaning that the effect of EMF exposure lasted for hours.

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PMID: 

Wei Sheng Yan Jiu. 2019 May ;48(3):482-487. PMID: 31133139

Abstract Title: 

[Chronotoxicity of 1.8 GHz radio-frequency radiation on plasma stress hormones and immune factors in mice].

Abstract: 

OBJECTIVE: To study the chronotoxicity of radio-frequency radiation(RF) on the plasma stress hormones and immune factors in mice.METHODS: A total of 72 healthy C57 BL mice with circadian rhythm were divided into twelve groups: 6 Sham group and 6 RF groups. RF groups were exposed to 1.8 GHz RF at 226μW/cm~2 for 60 days with 2 h/day respectively at corresponding zeitgeber time(ZT 0:00, ZT 4:00, ZT 8:00, ZT 12:00, ZT 16:00, ZT 20:00). The Sham group mice were exposed to the same condition without electromagnetic signal. At the end of last RF exposure, blood samples were collected from each animal. The concentrations of plasma stress hormones(ACTH, CORT) and immune factors(GM-CSF, TNF-α) were determined by enzyme linked immunosorbent assay(ELISA) method.RESULTS: The daily average levels of ACTH, CORT, GM-CSF and TNF-α were 84.12, 60.14, 1112.02 and 594.49 ng/L, which were decreased to 62.07, 41.21, 84.18 and 305.08 ng/L after 60 days of RF exposure. Compared to sham-exposed animals, the daily average levels of ACTH, CORT, GM-CSF and TNF-α were all significantly decreased(P0.05), circadian rhythms of ACTH was shifted in RF-exposed mice, with the amplitude reduced from 12.45 to 4.88 and peak time postponed from 1:39 to 5:29.CONCLUSION: 1.8 GHz RF may weaken the function of stress and immune, and disturb their circadian rhythmicities.

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PMID: 

Sheng Li Xue Bao. 2019 Jun 25 ;71(3):388-394. PMID: 31218329

Abstract Title: 

[Extremely low frequency electromagnetic radiation enhanced energy metabolism and induced oxidative stress in Caenorhabditis elegans].

Abstract: 

The aim of this study was to determine the effects of extremely low frequency electromagnetic field (ELF-EMF) on energy metabolism and oxidative stress in Caenorhabditis elegans (C. elegans). Worms in three adult stages (young adult stage, egg-laying stage and peak egg-laying stage) were investigated under 50 Hz, 3 mT ELF-EMF exposure. ATP levels, ATP synthase activity in vivo, reactive oxygen species (ROS) content, and changes of total antioxidant capacity (TAC) were detected, and worms' oxidative stress responses were also evaluated under ELF-EMF exposure. The results showed that ATP levels were significantly increased under this ELF-EMF exposure, and mitochondrial ATP synthase activity was upregulated simultaneously. In young adult stage, worms' ROS level was significantly elevated, together with upregulated TAC but with a decreased ROS-TAC score indicated by principal component analysis. ROS level and TAC of worms had no significant changes in egg-laying and peak egg-laying stages. Based on these results, we concluded that ELF-EMF can enhance worm energy metabolism and elicit oxidative stress, mainly manifesting as ATP and ROS level elevation together with ATP synthase upregulation and ROS-TAC score decrease in young adult C. elegans.

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